Oncotarget

Research Papers:

CD200Fc reduces LPS-induced IL-1β activation in human cervical cancer cells by modulating TLR4-NF-κB and NLRP3 inflammasome pathway

Aiqin He, Jia Shao, Yu Zhang, Hong Lu, Zhijun Wu and Yunzhao Xu _

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Oncotarget. 2017; 8:33214-33224. https://doi.org/10.18632/oncotarget.16596

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Abstract

Aiqin He1, Jia Shao1, Yu Zhang1, Hong Lu1, Zhijun Wu1, Yunzhao Xu2

1Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China

2Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, China

Correspondence to:

Zhijun Wu, email: wuzhijunnt@163.com

Yunzhao Xu, email: xuyunzhaonantong@163.com

Keywords: CD200Fc, cervical cancer, TLR4-NF-κB, NLRP3 inflammasome, IL-1β

Received: January 04, 2017     Accepted: March 16, 2017     Published: March 27, 2017

ABSTRACT

Chronic inflammation plays an important role in tumorigenesis of cervical cancer. CD200Fc, a CD200R1 agonist, has been found to have anti-inflammatory effects in autoimmune diseases and neuro-degeneration. However, the anti-inflammatory effect of CD200Fc on cervical cancer has not yet to be completely understood. This study investigated the anti-inflammatory effects and mechanisms of CD200Fc in LPS-induced human SiHa cells and Caski cells. SiHa cells and Caski cells were stimulated with 40 μg/ml LPS under different concentrations of CD200Fc for 90 min or 12 hours. The mRNA and protein levels of pro-IL-1β, cleaved-IL-1β and NLRP3, as well as the protein level of cleaved caspase-1, were significantly increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not change ASC and pro-caspase-1 expression. CD200Fc down-regulated protein expression of cleaved caspase-1 and mRNA and protein expression of pro-IL-1β, cleaved-IL-1β and NLRP3. In addition, the protein levels of TLR4, p-P65 and p-IκB, as well as the translocation of P65 to nucleus, were significantly increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not change t-P65 and t-IκB on protein levels, which were components of TLR-NF-κB pathway. CD200Fc down-regulated protein expression of TLR4, p-P65 and p-IκB and inhibited the translocation of P65 to nucleus in LPS-induced SiHa cells and Caski cells. These results indicated that CD200Fc appeared to suppress the inflammatory activity of TLR4-NF-κB and NLRP3 inflammasome pathway in LPS-induced SiHa cells and Caski cells. It provided novel mechanistic insights into the potential therapeutic uses of CD200Fc for cervical cancer.


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